title: S-sulfhydration/desulfhydration and S-nitrosylation/denitrosylation: a common paradigm for gasotransmitter signaling by H2S and NO.
abstract: Sulfhydryl groups on protein Cys residues undergo an array of oxidative reactions and modifications, giving rise to a virtual redox zip code with physiological and pathophysiological relevance for modulation of protein structure and functions. While over two decades of studies have established NO-dependent S-nitrosylation as ubiquitous and fundamental for the regulation of diverse protein activities, proteomic methods for studying H2S-dependent S-sulfhydration have only recently been described and now suggest that this is also an abundant modification with potential for global physiological importance. Notably, protein S-sulfhydration and S-nitrosylation bear striking similarities in terms of their chemical and biological determinants, as well as reversal of these modifications via group-transfer to glutathione, followed by the removal from glutathione by enzymes that have apparently evolved to selectively catalyze denitrosylation and desulfhydration. Here we review determinants of protein and low-molecular-weight thiol S-sulfhydration/desulfhydration, similarities with S-nitrosylation/denitrosylation, and methods that are being employed to investigate and quantify these gasotransmitter-mediated cell signaling systems.
authors.affiliation: Department of Pharmacology, Weill Cornell College of Medicine, 1300 York Avenue, New York, NY, USA.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Lu
authors.forename: Adam
authors.initials: A
authors.lastname: Kavalier
authors.forename: Eugene
authors.initials: E
authors.lastname: Lukyanov
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gross
mesh_terms: D000818:Animals; D002846:Chromatography, Affinity / Q000592:standards; D003545:Cysteine / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D064426:Gasotransmitters / Q000502:physiology; D019803:Glutathione Disulfide / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012015:Reference Standards; D026403:S-Nitrosothiols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D013194:Staining and Labeling; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D064426:Gasotransmitters; D020543:Proteome; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D003545:Cysteine; D019803:Glutathione Disulfide; D006862:Hydrogen Sulfide
keywords: (N-[(6-biotinamido) hexyl]-3′-(2′-pyridyldithio) propionamide); 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide; Biotin Switch; Biotin-HPDP; CBS; CSE; Cysteine; ETHE1; GSNO; GSSH; Glutathione; Hydrogen sulfide; MMTS; MS/MS; MST; Nitric oxide; Persulfide; S-nitrosoglutathione; SH; SNOSID; SQR; SRB; Sulfhydration; Sulfhydryl; TST; carboxy-PTIO; cystathionine β-synthase; cystathionine γ-lyase; glutathione persulfide; mercaptopyruvate sulfurtransferase; methyl methane thiosulfonate; persulfide dioxygenase; sulfate reducing bacteria; sulfide quinone reductase; tandem mass spectrometry; thiol; thiosulfate sulfur transferase (a.k.a. rhodanese)